Inferring human population size and separation history from multiple genome sequences.

Schiffels S, Durbin R - Nat. Genet. (2014)

Bottom Line:
The availability of complete human genome sequences from populations across the world has given rise to new population genetic inference methods that explicitly model ancestral relationships under recombination and mutation.The multiple sequentially Markovian coalescent (MSMC) analyzes the observed pattern of mutations in multiple individuals, focusing on the first coalescence between any two individuals.Results from applying MSMC to genome sequences from nine populations across the world suggest that the genetic separation of non-African ancestors from African Yoruban ancestors started long before 50,000 years ago and give information about human population history as recent as 2,000 years ago, including the bottleneck in the peopling of the Americas and separations within Africa, East Asia and Europe.

ABSTRACTThe availability of complete human genome sequences from populations across the world has given rise to new population genetic inference methods that explicitly model ancestral relationships under recombination and mutation. So far, application of these methods to evolutionary history more recent than 20,000-30,000 years ago and to population separations has been limited. Here we present a new method that overcomes these shortcomings. The multiple sequentially Markovian coalescent (MSMC) analyzes the observed pattern of mutations in multiple individuals, focusing on the first coalescence between any two individuals. Results from applying MSMC to genome sequences from nine populations across the world suggest that the genetic separation of non-African ancestors from African Yoruban ancestors started long before 50,000 years ago and give information about human population history as recent as 2,000 years ago, including the bottleneck in the peopling of the Americas and separations within Africa, East Asia and Europe.

Figure 4: Genetic Separation between population pairs(a) Relative cross coalescence rates in and out of Africa. African/Non-African pairs are shown in red colors, pairs within Africa in Purple colors. (b) Relative cross coalescence rates between populations outside Africa. European/East-Asian pairs in blue colors, Asian/MXL pairs in green colors, and other non-African pairs in other colors as indicated. The pairs that include MXL are masked to include only the putative Native American components. The most recent population separations are inferred from eight haplotypes, i.e. four haplotypes from each population, as indicated in the legend. (c) Comparison of the African/Non-African split with simulations of clean splits. We simulated three scenarios, at split times 50kya, 100kya and 150kya. The comparison demonstrates that the history of relative cross coalescence rate between African and Non-African ancestors is incompatible with a clean split model, and suggests it progressively decreased from beyond 150kya to approximately 50kya. (d) Schematic representation of population separations. Timings of splits, population separations, gene flow and bottlenecks are schematically shown along a logarithmic axis of time. Data for this Figure is available via Supplementary Table 5.

Mentions:
MSMC lets us explicitly study the genetic separation between two populations as a function of time by modeling the relationship of multiple haplotypes, half of which are from one population, and half from the other. As shown in Figure 4a, from analyzing four haplotypes for each pair of populations, we find that all relative cross coalescence rates between any non-African population and Yoruba are very similar and exhibit a slow gradual decline beginning earlier than 200kya and lasting until about 40kya. This similarity gives additional information beyond that from population size estimates, consistent with all non-African populations diverging as a single population from the Yoruban ancestors.

Figure 4: Genetic Separation between population pairs(a) Relative cross coalescence rates in and out of Africa. African/Non-African pairs are shown in red colors, pairs within Africa in Purple colors. (b) Relative cross coalescence rates between populations outside Africa. European/East-Asian pairs in blue colors, Asian/MXL pairs in green colors, and other non-African pairs in other colors as indicated. The pairs that include MXL are masked to include only the putative Native American components. The most recent population separations are inferred from eight haplotypes, i.e. four haplotypes from each population, as indicated in the legend. (c) Comparison of the African/Non-African split with simulations of clean splits. We simulated three scenarios, at split times 50kya, 100kya and 150kya. The comparison demonstrates that the history of relative cross coalescence rate between African and Non-African ancestors is incompatible with a clean split model, and suggests it progressively decreased from beyond 150kya to approximately 50kya. (d) Schematic representation of population separations. Timings of splits, population separations, gene flow and bottlenecks are schematically shown along a logarithmic axis of time. Data for this Figure is available via Supplementary Table 5.

Mentions:
MSMC lets us explicitly study the genetic separation between two populations as a function of time by modeling the relationship of multiple haplotypes, half of which are from one population, and half from the other. As shown in Figure 4a, from analyzing four haplotypes for each pair of populations, we find that all relative cross coalescence rates between any non-African population and Yoruba are very similar and exhibit a slow gradual decline beginning earlier than 200kya and lasting until about 40kya. This similarity gives additional information beyond that from population size estimates, consistent with all non-African populations diverging as a single population from the Yoruban ancestors.

Bottom Line:
The availability of complete human genome sequences from populations across the world has given rise to new population genetic inference methods that explicitly model ancestral relationships under recombination and mutation.The multiple sequentially Markovian coalescent (MSMC) analyzes the observed pattern of mutations in multiple individuals, focusing on the first coalescence between any two individuals.Results from applying MSMC to genome sequences from nine populations across the world suggest that the genetic separation of non-African ancestors from African Yoruban ancestors started long before 50,000 years ago and give information about human population history as recent as 2,000 years ago, including the bottleneck in the peopling of the Americas and separations within Africa, East Asia and Europe.

ABSTRACTThe availability of complete human genome sequences from populations across the world has given rise to new population genetic inference methods that explicitly model ancestral relationships under recombination and mutation. So far, application of these methods to evolutionary history more recent than 20,000-30,000 years ago and to population separations has been limited. Here we present a new method that overcomes these shortcomings. The multiple sequentially Markovian coalescent (MSMC) analyzes the observed pattern of mutations in multiple individuals, focusing on the first coalescence between any two individuals. Results from applying MSMC to genome sequences from nine populations across the world suggest that the genetic separation of non-African ancestors from African Yoruban ancestors started long before 50,000 years ago and give information about human population history as recent as 2,000 years ago, including the bottleneck in the peopling of the Americas and separations within Africa, East Asia and Europe.